A Review of Stem Cell Therapy in Ischemic Stroke

Published: 2021-07-28 20:30:07
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ABSTRACT
Stroke is a leading cause of death and disability. Effecting over 15 million people worldwide. Of those 15 million cases 5 million will die and a further 5 million will be left disabled. Currently there is little to no treatment for stroke, this leaves patients with a large deficit of treatment. Thus, there is a pressing need for new and effective treatment option. Stem cell therapy (SCT) is a well-established treatment method that has proved its self in other hematological diseases. This fact coupled with some promising results shown from animal models that show significant functional benefits have led research to the bedside. This review provides a brief history and scientific background to the stem cell therapy of ischemic stroke (IS). This will then be followed up with evidence of current clinical trials including a discussion of the various route of delivery, cell type, timing of treatment and number of cells used. Finally, the review will end with a discussion of what will become of stem cell therapy in the distant future.
INTRODUCTION
Stroke is a major cause of serious disability and the second largest cause of death in the world. Stroke is also very expensive taking up to 2-4% of all healthcare costs. Even if the age specific strokes stay constant or decrees slightly the number of new cases of stroke will rise each year with the advent of the ageing era. Stroke has been categorized as 1) ischemic (obstruction); 2) hemorrhagic (bleeding); 3) transient (transient ischemic attack) by the American Heart assertion, with ischemic stroke accounting for 85% of all stroke cases [3] it will be focus of this review. An ischemic stroke results from artery occlusion in the brain, which if left untreated will lead to cell death in the affected part of the brain. Current treatment of (IS) Is to use tissue plasminogen activator (t-PA) a medication that can help remove the clot in the brain. Unfortunately, this medication is only useful if administered within 3-4.5 hours after the stroke [5]. Aspirin can also be used as a deterrent to stroke but only provides a 1% absolute reduction in death and recurrent (IS) [1]. Most patients over time show some spontaneous recovery after stroke. This recovery can be attributed to cell regeneration in the brain, this regeneration until recently was thought to be impossible. This process of cell recovery has been named neurogenesis [2,3]. However, this recovery is often incomplete. Creating a need for further cell recovery in the brain. This with the evidence of neurogenesis have sparked the creation of experimental work investigation cell transplantation therapy in (IS).
Background and developments in Stem Cell therapy for Ischemic stroke
The clinic approaches of (SCT) can be divided into endogenous and exogenous approaches. The endogenous approach aims to stimulate the stem cells already present within the induvial. This uses a granulocyte-colony stimulating factor (G-CSF) which is used to mobilize stem cells for transplantation in hematological damaged areas [5,6]. This has shown promising results in animal studies showing direct benefits in cognitive regeneration. Several phase II trials are currently underway to investigate its efficacy in (IS). The exogenous approach involves the transplantation of stem cells directly into the damage area. This involve in vitro culture of cells and cell expansion prior to admission. This review will focus on the studies using exogenous approaches to (SCT) in (IS), as it is seeing a lot more focus from the stem cell community.
Following a stroke, both neural and supportive brain tissue elements are lost, unlike other neurogenerative disease that target a specific neuronal type. SCT for IS, therefore focuses on regenerative strategies to restore both neurol elements but supportive elements as well such as blood vessels. Many stem cells have been tested and evaluated in humans for their potentials in this use.
Neural stem cells (NSC)
It now generally accepted that neurogenesis originated from neural stem cells (NSC) that are located in specific regions of the adult mammalian brain. Throughout life creating new populations of neurons [17]. NSC can be isolated for fetal and adult mammalian brains. Multiply studies have shown isolation of NCS from adult rodent brains [18,19], and also a newer study has moved on to isolation in the human brain [20,21]. Preclinical studies explore the feasibility of using NSC’s to treat IS. When giving NSC through intravenous or stereotactically route the NSC have been shown to survive, migrate towards the lesion and differentiate, while promoting tissue repair, consequently improved neurological function and recovery in ischemic rodent [15,16]. Studies have shown that delayed intravenous transplantation of NSC at 3 days after ischemic stroke exhibited delayed neuroprotection by suppressing inflammation and focal glial scar formation, suggesting that NSCs had the potential to extend the therapeutic time window for ischemic stroke treatment [21]. There is currently a phase trial planned using commercial derived NSC named CTX to be delivered by stereotactic injection in patients with IS. While NSC show promise the practicability of routine brain biopsies for isolation of adult human NSC is not, leading many researchers to exploring other methods of SCT with cells that are more accessible.
Bone marrow derived stem cells
Bone marrow derived stem cells consist of both hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC). HSCs are the precursors of all the blood and lymphoid cell lineages. MSCs give rise the stromal cells of the bone marrow. The stromal cells consist of chondrocytes, adipocytes and osteoblasts. Bone marrow is an attractive choice for isolating stem cells for being easily accessible, autologous (coming from the same individual) meaning there would be no need for immunosuppressant medication. Bone marrow cells have been shown to migrate to the brain a dissociate into cells the express neuron-specific markers [37]. Both populations of bone marrow cells have been studied extensively on their potential for neuronal differentiation and possible use in neuroregenerative therapy.

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